Microneedle-mediated delivery of hydroxypropyl-β-cyclodextrin-encapsulated Angelica sinensis (Danggui) essential oil for acne treatment: efficacy and mechanisms.

Acne is a multifactorial dermatological condition driven by Propionibacterium acnes (P. acnes) infection, inflammation, and sebum dysregulation. While essential oils, such as Angelica sinensis (Danggui) essential oil (AEO), exhibit antimicrobial and anti-inflammatory properties, their clinical application is hindered by poor solubility, stability, and skin penetration. To address these limitations, we developed hydroxypropyl-β-cyclodextrin (HPCD)-complexed AEO-loaded microneedles (AEO@HPCD MNs) using hyaluronic acid for enhanced transdermal delivery. The optimized AEO@HPCD MNs demonstrated superior mechanical strength, rapid dissolution, and efficient cargo release. In vitro studies confirmed potent antibacterial activity against P. acnes, while in vivo experiments revealed significant reductions in acne lesion size and IL-1β levels. RNA sequencing of treated acne lesions identified key downregulated genes (Fpr1, Rarres2, Cxcl5, Gbp3, Hck, Gbp7, Librb4a, Psmb8) and enriched pathways, including innate immunity and inflammatory responses. Notably, AEO@HPCD MNs suppressed 5α-reductase and fatty acid synthase (FAS) expression, demonstrating-for the first time-AEO's ability to normalize sebum production. Mechanistically, AEO@HPCD MNs exert multifaceted therapeutic effects: (1) direct antibacterial activity against P. acnes, (2) suppression of inflammatory and immune-related pathways through modulation of Toll-like receptor, NOD-like receptor, and cytokine-cytokine receptor signaling pathways, (3) regulation of sebum production via lipid-metabolic gene expression modulation, and (4) enhanced delivery efficiency and microenvironment modification through the physical action of microneedles, collectively contributing to synergistic acne therapy. This study develops a microneedle delivery platform that addresses both essential oil instability and inclusion complex delivery challenges while targeting multiple acne pathogenic factors. The AEO@HPCD MNs provide a safe, minimally invasive, multifunctional therapeutic strategy for acne treatment.